Source Citation

Abstract

Question

In patients with suspected acute bleeding from esophageal varices, are somatostatin
or its analogues more effective than placebo or no treatment?

Methods

Data sources: MEDLINE (1966 to February 2004), the Cochrane Library, abstracts from conference proceedings,
reference lists of trials, and contact with authors.

Study selection and assessment: Randomized controlled trials (RCTs) in any language that compared somatostatin or
its analogues with placebo or no treatment in patients with suspected or recently
bleeding esophageal varices. Quality assessment of individual studies included allocation
concealment and blinding.

Main results

20 RCTs (n = 2518) met the selection criteria. 9 trials were high-quality, having concealed
allocation and blinding of clinicians and patients. Somatostatin did not reduce mortality
in all trials in which it was assessed (14 RCTs) or in high-quality trials (7 RCTs)
(Table). Patients receiving somatostatin required fewer units of blood products (Table).
Rebleeding rates were lower with somatostatin in low-quality trials but did not differ
from placebo or no treatment in high-quality trials (Table). Fewer patients receiving
somatostatin had failure of hemostasis (Table). Groups did not differ for balloon
tamponade (Table).

Conclusions

In patients with suspected acute bleeding from esophageal varices, somatostatin or
its analogues do not reduce mortality. Patients who receive somatostatin require fewer
units of blood products and have a lower failure rate of hemostasis.

Commentary

The meta-analysis by Gøtzsche and Hr&oacgr;bjartsson updates their previous meta-analysis
(1), attempting to determine benefits of somatostatin analogues for bleeding esophageal
varices. 8 recent studies added to their previous analysis showed no significant differences.
All studies to date were subdivided on the basis of high- versus low-quality; high-quality
studies included concealed allocation and double-blind design. In the high-quality
studies, differences between somatostatin and placebo were even less significant—about
a half unit of blood was saved per patient with somatostatin treatment.

Research in the treatment of bleeding esophageal varices is complex and fraught with
confounding variables that contribute to both the intra- and inter-center differences seen in this review: 1) endoscopic criteria for diagnosis (affected
by the extent of the hemorrhage and visibility), 2) differing drug dosage and duration
of infusion, 3) varying protocols for intervention with definitive therapy, 4) definition
of rebleeding or failure of hemostasis (appearance of blood in nasogastric tube vs
endoscopic proof), 5) threshold for transfusion, 6) use of such alternative therapies
as endoscopic therapy or transjugular intrahepatic portalsystemic shunt (TIPS) in
patients who may or may not be potential liver transplantation candidates (in whom
earlier intervention is desirable), and 7) timing of assessment of mortality (5 to
42 d). In addition, the degree of the decompensation of cirrhosis at presentation
and the severity of coagulopathy contributing to the bleeding episodes were often
not satisfactorily quantified in the included studies. Of interest, even studies done
after the Baveno II Consensus Workshops (2) had some of these limitations, attesting to the difficult nature of the problem.

Somatostatin analogues have only marginal benefit in the management of bleeding varices,
as concluded in this meta-analysis. In my view, this is the final nail in the coffin
of their efficacy, and there is no basis to use or study this class of drug further
for bleeding varices. However, if the practicing physician chooses to use these drugs
as a temporizing measure while the patient is resuscitated during acute variceal hemorrhage,
it should not be done at the expense of delaying definitive treatment.